The peripheral blood of patients with infectious mononucleosis (IM) contains atypical lymphocytes which are capable of killing cell lines. In patients with IM caused by the Epstein Barr virus (EBV) a specific cytotoxic response has been identified which is directed against an EBV-associated antigen in infected B cells. However patients with IM caused by cytomegalovirus (CMV) also develop atypical lymphocytes capable of killing cultured cells. It is, therefore, suggested that part of the lymphocytosis characteristic of IM is not EBV specific but is generated by antigenic blast transformation in a manner analogous to induction of killer blast by mitogens. In support of this theory we have induced killer blasts with irradiated cell-free EBV in vitro cultures of lymphocytes from EBV seropositive donors. These cytotoxic cultures are being separated according to size by velocity sedimentation and their characteristics and functions determined. Comparison is made with cells from the blood of IM patients which have been similarly separated. These experiments should help elucidate the nature of the immune response in IM which is a self-limiting lymphoproliferative disorder and provide information more generally applicable to understanding the control of malignant proliferation.